Placental tissue enhances uterine relaxation by nitroglycerin.
Nitroglycerin (TNG) has recently gained popularity in obstetric anesthesia for facilitating acute uterine relaxation in the treatment of obstetric emergencies such as retained placenta. Laboratory investigations, however, have consistently found the uterus insensitive to clinically used doses of TNG. We hypothesized that the presence of the placenta in the uterus may be important for TNG to be effective, because it has been present in most clinical reports and has generally been absent in laboratory investigations. Sections of near-term gravid rat uteri were mounted for isometric force recording. We studied spontaneous contractions and acetylcholine-induced sustained contractions both with and without the addition of minced placental tissue in close approximation to the uterine muscle. Phenylephrine-precontracted rings of thoracic aorta were studied as a positive control. Log dose-response curves for TNG, 10(-9) to 10(-5) M, were constructed for each tissue. Uterine muscle alone was resistant to all but the largest doses of TNG, both in spontaneous and sustained contraction models. The addition of placental tissue caused a marked increase in sensitivity, reducing spontaneous uterine contractions by 50% at log -5.92 M (95% confidence interval, -6.49, -5.05), which was comparable to the sensitivity in aorta. Nitric oxide (NO) inhibitors pyrogallol (a superoxide anion generator) and methylene blue (a guanylate cyclase inhibitor) completely blocked the effect of TNG in the presence of placenta. Placental tissue modestly increased the response of aorta to TNG, but not of uterine tissue to the NO-independent uterine relaxants MgSO4 and terbutaline.


CONCLUSIONS
Nitroglycerin can relax the human uterus during obstetric emergencies, but the drug has never been proven effective in the laboratory. This study shows that nitroglycerin can relax uterine contractions in the rat, provided that the placenta is adjacent to the uterus. The mechanism seems to be via the release of nitric oxide.
Segal
S
S
Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115-6110, USA. bssegal@zeus.bwh.harvard.edu
Csavoy
A N
AN
Datta
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005260:Female; D005996:Nitroglycerin / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*
D010656:Phenylephrine; D005996:Nitroglycerin; D000109:Acetylcholine